Expression of ICAM‐R (ICAM‐3), a novel counter‐receptor for LFA‐1, in rheumatoid and nonrheumatoid synovium

Abstract

Objective. To study the distribution of intercellular adhesion molecule receptor (ICAM-R, or ICAM3), a novel ligand for the leukointegrin lymphocyte function-associated antigen 1 (LFA-l), in normal and rheumatoid synovial membranes and to compare this with the distribution of ICAM-1, ICAM-2, vascular cell adhesion molecule 1 (VCAM-l), and endothelial leukocyte adhesion molecule 1 (ELAM-1).Methods. We performed immunohistochemical analyses of frozen sections of normal and rheumatoid synovial tissue using monoclonal antibodies to the molecules examined.Results. ICAM-1 staining was detectable on the vascular endothelium and the synovial lining cells of both normal and rheumatoid synovial membranes. A variable proportion of lymphocytes infiltrating rheumatoid tissues expressed ICAM-1. ICAM-2 staining was demonstrable in the vascular endothelium of both normal and inflamed tissues, the latter demonstrating a significantly higher proportion of positive vessels. ELAM-1 staining was not detectable in normal synovial membranes but was seen on the endothelium of a limited number of rheumatoid synovial vessels, usually close to the synovial lining cell layer. VCAM-1 staining was intense in both normal and rheumatoid synovial lining cells, but vascular staining was weak in both. In conHani El-Gabalawy, MD: The University of Manitoba, Winnipeg, Manitoba, Canada; Michael Gallatin, PhD: ICOS Corporation, Seattle, Washington; Rosemay Vazeux, PhD: ICOS Corporation; Gary Peterman, PhD: ICOS Corporation; John Wilkins, P h D University of Manitoba.Address reprint requests to Hani El-Gabalawy, MD, Rheumatic Disease Unit, 800 Sherbrook Street, Winnipeg, Manitoba R3A 1M4, Canada.Submitted for publication March 31, 1993; accepted in revised form November 30, 1993. trast, ICAM-R staining was not detected in association with any synovial blood vessels, but was widely expressed by lymphocytes and macrophages. Cells of the lining layer did not stain for ICAM-R.Conclusion. Although ICAM-R is a ligand for LFA-1 and shares considerable sequence homology with ICAM-1 and ICAM-2, it does not appear to be expressed by the endothelium of normal or inflamed synovial vessels. Intense expression of ICAM-R by rheumatoid synovial lymphocytes and macrophages suggests that it may play a role in processes requiring cell-cell contact, such as antigen presentation and homotypic aggregation.Chronic inflammatory lesions such as rheumatoid synovitis require ongoing recruitment and retention of leukocytes from the vascular space. A critical initial step involves the adhesion of leukocytes to vascular endothelium (1-3). This is currently thought to be regulated by a cascade of molecular interactions occurring between leukocyte membrane receptors and endothelial counter-receptors, many of which are inducible in their expression. Several endothelial adhesion molecules have been well characterized and shown to participate in leukocyte attachment. These include the endothelial leukocyte adhesion molecule 1 (ELAM-1, or E-selectin) (4), intercellular adhesion molec...

Endothelial cells are the major source of sICAM-1 in rheumatoid synovial tissue

“…Cytospin preparations yielded immunohistochemical results in accordance with data obtained from cryosections: ICAM-1 was expressed within the enlarged synovial intima, the subsynovial region and the intima of blood vessels, whereas its expression in lymphocytic aggregates and follicles was low (with the exception of the follicular dendritic cells). Our findings are well in line with the results of others who have demonstrated a high expression of ICAM-1 on macrophage-like synovial cells and endothelial cells [6,7,9] and a paucity of ICAM-1 expression in lymphocyte-rich areas [9,25]. Some authors have also demonstrated expression of ICAM-1 on a high percentage of synovial fibroblasts cultured in vitro [6].…”

“…ICAM-1 (intercellular adhesion molecule-1 or CD54), which is an important adhesion molecule in inflammation [2,3], is thought to play a central role in this autoimmune process [4,5]. In several studies the tissue distribution, serum level and synovial fluid (SF) level of soluble ICAM-1 (sICAM-1) have been characterized in RA patients [6][7][8][9][10][11][12][13][14], but it is still unclear (a) which of the RS cells comprise the main source of sICAM-1 and (b) whether the elevated sICAM-1 levels seen in SF and serum originate in the RS. To our mind, an adequate approach to solving these problems is provided only by analysis of the sICAM-1-shedding capacity of RS.…”

Homing of mucosal leukocytes to joints. Distinct endothelial ligands in synovium mediate leukocyte-subtype specific adhesion.

“…This has indirectly implicated that the major endothelial ligands of these lymphocyte homing receptors (ICAM-1 or -2, VCAM-1, PNAd, and hyaluronate, respectively) may play a role in synovial adhesion. Indeed, blood vessels in heterogeneous materials of inflamed synovia have been shown to express VCAM-1, PNAd, E-and P-selectin, and ICAMs (16,17,(19)(20)(21)(22). This study is the first systematic effort to analyze the expression of all known endothelial adhesion molecules simultaneously in one series of specimens.…”

Synovial distribution of αd/CD18, a novel leukointegrin. Comparison with other integrins and their ligands

“…One of these sections was stained with hematoxylin and eosin (H&E) in order to properly orient the remainder of the sections. An avidin-biotin complex (ABC) method was used as previously described (24) and as detailed in previous immunohistochemical studies (18). As an antibody control, mouse plasma was substituted for the primary monoclonal antibodies.…”